The predictive role of soluble programmed death ligand 1 in digestive system cancers

IntroductionThe prognostic role of soluble programmed death ligand 1 (sPD-L1) in digestive system cancers (DSCs) remains inconclusive. This study aimed to explore the predictive value of sPD-L1 expression in DSCs.MethodsComprehensive searches were run on the electronic databases (PubMed, Web of Science, EMBASE, and the Cochrane Library) to identify studies that assessed the prognostic role of sPD-L1 in DSCs. Review Manager software (version 5.3) was used for all analyses. Pooled data for survival outcomes were measured as hazard ratios (HRs), 95% confidence intervals (CIs), and odds ratios and their 95% CIs.ResultsThe search identified 18 studies involving 2,070 patients with DSCs. The meta-outcome revealed that a high level of sPD-L1 was related to poorer overall survival (HR, 3.06; 95% CI: 2.22–4.22, p<0.001) and disease-free survival (HR, 2.53; 95% CI: 1.67–3.83, p<0.001) in DSCs. Individually, the prognostic significance of high level of sPD-L1 expression was the highest in hepatic cell carcinoma (HR, 4.76; p<0.001) followed by gastric cancer (HR=3.55, p<0.001).ConclusionsPD-L1 may be a prognostic factor in DSCs for overall survival and disease-free survival. Inflammatory cytokines, treatment approaches, and other factors may affect the expression of sPD-L1. Therefore, the prognostic value of sPD-L1 for recurrence and metastasis should be further investigated. sPD-L1 may also predict response to treatment. Well-designed prospective studies with standard assessment methods should be conducted to determine the prognostic value of sPD-L1 in DSCs

Survival impact of postoperative therapy modalities according to margin status in non–small cell lung cancer patients in the United States

Objective Unlike complete (R0) resection guidelines, current National Comprehensive Cancer Network (NCCN) adjuvant therapy guidelines after incomplete (R1/R2) resection of non–small cell lung cancer (NSCLC) are based on low-level evidence. We attempted to validate them. Methods Patients with pathologic stage I-IIIA NSCLC from 2004 to 2011 in the National Cancer Database were stratified by margin status, NCCN-specified stage groupings, and adjuvant therapy exposure (none, radiotherapy, chemotherapy, or both). Five-year overall survival (OS) and hazard ratios, adjusted for patient and institutional characteristics, were compared. We used a parallel analysis of R0 resections to validate our methodology. Results We analyzed 3461 R1/R2, and 78,979 R0 resections. After R0 resection, the NCCN-recommended option was associated with the best survival across all stage groups, supporting our analytic approach. Patients with R1/R2 stage IA treated with radiation had a 26% OS, compared with 58% with no treatment (P = .003). In patients with stage IB/IIA(N0) R1/R2, radiation was associated with a 25% OS compared with 47% with no treatment (P = .025) and 62% with chemotherapy (P < .007). Chemoradiation was not associated with a survival benefit in either group. Patients with IIA(N1)/IIB and IIIA had better survival with chemotherapy or chemoradiation. No group had a survival benefit with radiation alone. Conclusions NCCN adjuvant therapy guidelines after complete resection, based on high-level evidence, are validated, but not guidelines for patients with incompletely resected early-stage NSCLC, which are based on low-level evidence. Monomodality postoperative radiotherapy was not validated for any stage. Specific studies are needed to determine optimal management after incomplete resection

Dynamic tilt testing of MEMS inclinometers based on conical motions

The MEMS inclinometer integrates a tri-axis accelerometer and a tri-axis gyroscope to solve the perceived dynamic inclinations through a complex data fusion algorithm, which has been widely used in the fields of industrial, aerospace, and monitoring. In order to ensure the validity of the measurement results of MEMS inclinometers, it is necessary to determine their dynamic performance parameters. This study proposes a conical motion-based MEMS inclinometer dynamic testing method, and the motion includes the classical conical motion, the attitude conical motion, and the dual-frequency conical motion. Both the frequency response and drift angle of MEMS inclinometers can be determined. Experimental results show that the conical motions can accelerate the angle drift of MEMS inclinometers, which makes them suitable for dynamic testing ofMEMSinclinometers. Additionally, the tilt sensitivity deviation of theMEMS inclinometer by the proposed method and the turntable-based method is less than 0.26 dB.We further provide the research for angle drift and provide discussion

Radiation produces differential changes in cytokine profiles in radiation lung fibrosis sensitive and resistant mice

<p>Abstract</p> <p>Background</p> <p>Recent research has supported that a variety of cytokines play important roles during radiation-induced lung toxicity. The present study is designed to investigate the differences in early cytokine induction after radiation in sensitive (C57BL/6) and resistant mice (C3H).</p> <p>Results</p> <p>Twenty-two cytokines in the lung tissue homogenates, bronchial lavage (BAL) fluids, and serum from 3, 6, 12, 24 hrs to 1 week after 12 Gy whole lung irradiation were profiled using a microsphere-based multiplexed cytokine assay. The majority of cytokines had similar baseline levels in C57BL/6 and C3H mice, but differed significantly after radiation. Many, including granulocyte colony-stimulating factor (G-CSF), interleukin-6 (IL-6), and keratinocyte-derived chemokine (KC) were elevated significantly in specimens from both strains. They usually peaked at about 3–6 hrs in C57BL/6 and 6–12 hrs in C3H. At 6 hrs in lung tissue, G-CSF, IL-6, and KC increased 6, 8, and 11 fold in C57BL/6 mice, 4, 3, and 3 fold in the C3H mice, respectively. IL-6 was 10-fold higher at 6 hrs in the C57BL/6 BAL fluid than the C3H BAL fluid. MCP-1, IP-10, and IL-1α also showed some differences between strains in the lung tissue and/or serum. For the same cytokine and within the same strain of mice, there were significant linear correlations between lung tissue and BAL fluid levels (R²ranged 0.46–0.99) and between serum and tissue (R²ranged 0.56–0.98).</p> <p>Conclusion</p> <p>Radiation induced earlier and greater temporal changes in multiple cytokines in the pulmonary fibrosis sensitive mice. Positive correlation between serum and tissue levels suggests that blood may be used as a surrogate marker for tissue.</p

Modern Radiation Further Improves Survival in Non-Small Cell Lung Cancer: An Analysis of 288,670 Patients

Background: Radiation therapy plays an increasingly important role in the treatment of patients with non-small-cell lung cancer (NSCLC). The purpose of the present study is to assess the survival outcomes of radiotherapy treatment compared to other treatment modalities and to determine the potential role of advanced technologies in radiotherapy on improving survival. Methods: We used cancer incidence and survival data from the Surveillance, Epidemiology, and End Results database linked to U.S. Census data to compare survival outcomes of 288,670 patients with stage I-IV NSCLC treated between 1999 and 2008. The primary endpoint was overall survival. Results: Among the 288,670 patients diagnosed with stage I-IV NSCLC, 92,374 (32%) patients received radiotherapy-almost double the number receiving surgery (51,961, 18%). Compared to other treatment groups and across all stages of NSCLC, patients treated with radiotherapy showed greater median and overall survival than patients without radiation treatment (p < 0.0001). Radiotherapy had effectively improved overall survival regardless of age, gender, and histological categorization. Radiotherapy treatment received during the recent time period 2004 - 2008 is correlated with enhanced survival compared to the earlier time period 1999 - 2003. Conclusion: Radiation therapy was correlated with increased overall survival for all patients with primary NSCLC across stages. Combined surgery and radiotherapy treatment also correlates with improved survival, signaling the value of bimodal or multimodal treatments. Population-based increases in overall survival were seen in the recent time period, suggesting the potential role of advanced radiotherapeutic technologies in enhancing survival outcomes for lung cancer patients

Machine Learning to Build and Validate a Model for Radiation Pneumonitis Prediction in Patients with Non–Small Cell Lung Cancer

Purpose: Radiation pneumonitis is an important adverse event in patients with non–small cell lung cancer (NSCLC) receiving thoracic radiotherapy. However, the risk of radiation pneumonitis grade ≥ 2 (RP2) has not been well predicted. This study hypothesized that inflammatory cytokines or the dynamic changes during radiotherapy can improve predictive accuracy for RP2. Experimental Design: Levels of 30 inflammatory cytokines and clinical information in patients with stages I–III NSCLC treated with radiotherapy were from our prospective studies. Statistical analysis was used to select predictive cytokine candidates and clinical covariates for adjustment. Machine learning algorithm was used to develop the generalized linear model for predicting risk RP2. Results: A total of 131 patients were eligible and 17 (13.0%) developed RP2. IL8 and CCL2 had significantly (Bonferroni) lower expression levels in patients with RP2 than without RP2. But none of the changes in cytokine levels during radiotherapy was significantly associated with RP2. The final predictive GLM model for RP2 was established, including IL8 and CCL2 at baseline level and two clinical variables. Nomogram was constructed based on the GLM model. The model's predicting ability was validated in the completely independent test set (AUC = 0.863, accuracy = 80.0%, sensitivity = 100%, specificity = 76.5%). Conclusions: By machine learning, this study has developed and validated a comprehensive model integrating inflammatory cytokines with clinical variables to predict RP2 before radiotherapy that provides an opportunity to guide clinicians

Shared and Distinct Neural Bases of Large- and Small-Scale Spatial Ability: A Coordinate-Based Activation Likelihood Estimation Meta-Analysis

Background: Spatial ability is vital for human survival and development. However, the relationship between large-scale and small-scale spatial ability remains poorly understood. To address this issue from a novel perspective, we performed an activation likelihood estimation (ALE) meta-analysis of neuroimaging studies to determine the shared and distinct neural bases of these two forms of spatial ability.Methods: We searched Web of Science, PubMed, PsycINFO, and Google Scholar for studies regarding “spatial ability” published within the last 20 years (January 1988 through June 2018). A final total of 103 studies (Table 1) involving 2,085 participants (male = 1,116) and 2,586 foci were incorporated into the meta-analysis.Results: Large-scale spatial ability was associated with activation in the limbic lobe, posterior lobe, occipital lobe, parietal lobe, right anterior lobe, frontal lobe, and right sub-lobar area. Small-scale spatial ability was associated with activation in the parietal lobe, occipital lobe, frontal lobe, right posterior lobe, and left sub-lobar area. Furthermore, conjunction analysis revealed overlapping regions in the sub-gyrus, right superior frontal gyrus, right superior parietal lobule, right middle occipital gyrus, right superior occipital gyrus, left inferior occipital gyrus, and precuneus. The contrast analysis demonstrated that the parahippocampal gyrus, left lingual gyrus, culmen, right middle temporal gyrus, left declive, left superior occipital gyrus, and right lentiform nucleus were more strongly activated during large-scale spatial tasks. In contrast, the precuneus, right inferior frontal gyrus, right precentral gyrus, left inferior parietal lobule, left supramarginal gyrus, left superior parietal lobule, right inferior occipital gyrus, and left middle frontal gyrus were more strongly activated during small-scale spatial tasks. Our results further indicated that there is no absolute difference in the cognitive strategies associated with the two forms of spatial ability (egocentric/allocentric).Conclusion: The results of the present study verify and expand upon the theoretical model of spatial ability proposed by Hegarty et al. Our analysis revealed a shared neural basis between large- and small-scale spatial abilities, as well as specific yet independent neural bases underlying each. Based on these findings, we proposed a more comprehensive version of the behavioral model